PubMed Health⌕ Search

Biomedical subjects

J B Hermiller

Publications and source records attributed to J B Hermiller.

At least 19 recordsLinked to original sources
PubMed2006

The safety and efficacy of the StarClose Vascular Closure System: the ultrasound substudy of the CLIP study.

BACKGROUND: The StarClose Vascular Closure System (Abbott Vascular, Redwood City, CA) features a nitinol clip that is designed to achieve closure of the femoral arteriotomy access site. The CLIP Study was performed to assess the safety and efficacy of StarClose when compared with standard manual compression following 5-6 French diagnostic or interventional percutaneous procedures. A substudy of this trial was designed to assess the utility of duplex ultrasonography to assess patency of the femoral artery and to determine access site complications (pseudoaneurysm, arteriovenous fistula, hematoma, deep vein thrombosis) in a multicenter prospective trial. This is the report of the duplex ultrasound (DUS) substudy of the CLIP trial. METHODS: A total of 17 U.S. sites enrolled 596 subjects with 483 subjects randomized at a 2:1 ratio to receive StarClose or manual compression of the arteriotomy after a percutaneous procedure. The study included roll-in (n = 113), diagnostic (n = 208), and interventional (n = 275) arms with a primary safety endpoint of major vascular complications through 30 days and a primary efficacy endpoint of postprocedure time to hemostasis. A substudy of the CLIP interventional arm evaluated DUS images of the closure site at five study sites, targeting 100 subjects at day 30 following hemostasis. The DUS protocol was devised and implemented by an independent vascular ultrasound core laboratory with extensive experience in vascular device trials. DUS inguinal region from 6 cm proximal to 6 cm distal to the arteriotomy puncture was performed. A qualitative examination was performed to determine the presence of iatrogenic vascular injuries: hematoma, pseudoaneurysm (PSA), arteriovenous fistula (AVF), and arterial/venous thrombosis or stenosis using 2-dimensional gray scale, color, and focused Doppler images. RESULTS: DUS of 96 subjects randomized to StarClose (n = 71) and compression (n = 25) were performed and evaluated. There was no evidence of hematoma, PSA, or AVF observed in the StarClose group. No StarClose subjects in the substudy had a PSA or AVF. All patients in the substudy demonstrated patency of the access site artery and vein without thrombosis or stenosis. Finally, in the entire study cohort, no clinically-driven DUS studies demonstrated iatrogenic vascular injury or vessel thrombosis in the StarClose treated patients. CONCLUSION: DUS, a safe and reliable method for determining the safety and efficacy of access site closure devices, is a reliable, safe, inexpensive and accurate method of assessing vascular access site complications in multicenter trials. In this substudy of the CLIP study, DUS found no statistical difference in access site complications between the StarClose and manual compression groups. Both groups maintained vessel patency without stenosis, thrombosis, hematoma, pseudoaneurysm, or AV fistula.

Adult↗
PubMed2006

The StarClose Vascular Closure System: interventional results from the CLIP study.

BACKGROUND: The StarClose Vascular Closure System is a femoral access site closure technology that uses a flexible nitinol clip to complete a circumferential, extravascular arteriotomy close. The Clip CLosure In Percutaneous Procedures study was initiated to study the safety and efficacy of the StarClose device in subjects undergoing diagnostic and interventional catheterization procedures. METHODS: A total of 17 U.S. sites enrolled 596 subjects, with 483 subjects randomized at a 2:1 ratio to receive StarClose or standard compression of the arteriotomy after the percutaneous procedure. The study included roll-in (n = 113), diagnostic (n = 208), and interventional (n = 275) arms with a primary safety endpoint of major vascular complications through 30 days and a primary efficacy endpoint of postprocedure time to hemostasis. RESULTS: The results of the diagnostic StarClose cohort have been reported separately. Results for the interventional arm revealed major vascular complications occurring in 1.1% of StarClose subjects (2/184) and 1.1% in manual compression subjects (1/91; P = 1.00). No infections were seen in either cohort. Minor complications in the StarClose interventional group occurred at a rate of 4.3% (8/184) and with compression at 9.9% (9/91; P = 0.107). Pseudoaneurysm or arteriovenous fistula was not seen with StarClose. With StarClose, procedural success was 100% (136/136) for the diagnostic group and 98.9% (181/183) in the interventional group. Device success for the treatment group was 86.8%. In the interventional cohort, 87.3% (158/181) of StarClose subjects reported a pain scale of 0-3 compared with 93.3% (84/90) in the compression group, which was not statistically different. CONCLUSIONS: The clinical results of this study demonstrate that the StarClose Vascular Closure System is noninferior to manual compression with respect to the primary safety endpoint of major vascular events in subjects who undergo percutaneous interventional procedures. StarClose significantly reduced time to hemostasis, ambulation, and dischargeability when compared with compression.

Aged↗
PubMed2001

Design of the therapeutic angiogenesis with recombinant fibroblast growth factor-2 for intermittent claudication (TRAFFIC) trial.

The Therapeutic Angiogenesis With Recombinant Fibroblast Growth Factor-2 for Intermittent Claudication (TRAFFIC) is a large, randomized, placebo-controlled, regimen-finding trial of intra-arterial recombinant fibroblast growth factor-2 in patients with intermittent claudication. This report describes the major design considerations and end points in TRAFFIC.

Double-Blind Method↗
PubMed2001

Final results of a randomized trial comparing the NIR stent to the Palmaz-Schatz stent for narrowings in native coronary arteries.

The NIR stent is a novel second generation tubular stent that was designed to overcome some of the limitations of the earlier Palmaz-Schatz (PS) stent design. The NIR Vascular Advanced North American (NIRVANA) trial randomized 849 patients with single coronary lesions to treatment with the NIR stent or the PS stent. The study was an "equivalency" trial, designed to demonstrate that the NIR stent was not inferior to (i.e., equivalent or better than) the PS stent, for the primary end point of target vessel failure (defined as death, myocardial infarction, or target vessel revascularization) by 9 months. Successful stent delivery was achieved in 100% versus 98.8%, respectively, with a slightly lower postprocedural diameter stenosis (7% vs. 9%, p = 0.04) after NIR and PS stent placement, respectively. Major adverse cardiac events (death, myocardial infarction, repeat target lesion revascularization) were not different at 30 days (4.3% vs. 4.4%). The primary end point of target vessel failure at 9 months was seen in 16.0% of NIR versus 17.2% of PS patients, with the NIR proving to be equal or superior to the PS stent (p <0.001 by test for equivalency). Angiographic restudy in 71% of a prespecified cohort showed no significant difference in restenosis (19.3% vs 22.4%). Thus, the NIR stent showed excellent deliverability with slightly better acute angiographic results and equivalent or better 9-month target vessel failure rate when compared with the PS stent.

Aged↗
PubMed2000

Randomized trial of contrast media utilization in high-risk PTCA: the COURT trial.

BACKGROUND: Previous in vitro and in vivo studies have suggested an association between thrombus-related events and type of contrast media. Low osmolar contrast agents appear to improve the safety of diagnostic and coronary artery interventional procedures. However, no data are available on PTCA outcomes with an isosmolar contrast agent. METHODS AND RESULTS: A multicenter prospective randomized double-blind trial was performed in 856 high-risk patients undergoing coronary artery intervention. The objective was to compare the isosmolar nonionic dimer iodixanol (n=405) with the low osmolar ionic agent ioxaglate (n=410). A composite variable of in-hospital major adverse clinical events (MACE) was the primary end point. A secondary objective was to evaluate major angiographic and procedural events during and after PTCA. The composite in-hospital primary end point was less frequent in those receiving iodixanol compared with those receiving ioxaglate (5.4% versus 9.5%, respectively; P=0.027). Core laboratory defined angiographic success was more frequent in patients receiving iodixanol (92.2% versus 85. 9% for ioxaglate, P=0.004). There was a trend toward lower total clinical events at 30 days in patients randomized to iodixanol (9.1% versus 13.2% for ioxaglate, P=0.07). Multivariate predictors of in-hospital MACE were use of ioxaglate (P=0.01) and treatment of a de novo lesion (P=0.03). CONCLUSIONS: In this contemporary prospective multicenter trial of PTCA in the setting of acute coronary syndromes, there was a low incidence of in-hospital clinical events for both treatment groups. The cohort receiving the nonionic dimer iodixanol experienced a 45% reduction in in-hospital MACE when compared with the cohort receiving ioxaglate.

Aged↗
PubMed2000

Efficacy of abciximab readministration in coronary intervention.

Abciximab, an Fab monoclonal antibody fragment that blocks the platelet glycoprotein IIb/IIIa receptor, is increasingly used as an adjunct to coronary intervention. Little is known, however, about the efficacy and safety of readministration of abciximab. This study examined and characterized outcomes of patients receiving abciximab for a second time. From April 1995 to June 1997, 164 consecutive patients were readministered abciximab at our 3 institutions. We retrospectively examined and analyzed in-hospital outcomes in this cohort. The median time to readministration was 95 days. The angiographic success rate of percutaneous intervention was 99.5%. Rates and 95% confidence intervals of in-hospital events were death 2% (0.7% to 6.1%), myocardial infarction 3% (1% to 7%), coronary bypass surgery 0% (0% to 2.2%), and intracranial hemorrhage 2% (0.4% to 5.3%). Severe thrombocytopenia was observed in 4% of patients (1.4% to 7.8%) after readministration. Allergic or anaphylactic reactions were not observed. Major bleeding was associated with excessive concomitant antithrombotic therapy. Patients undergoing readministration of abciximab within 2 weeks of first administration experienced a higher incidence of severe thrombocytopenia (12% vs. 2%, p = 0.046). Thus, abciximab remains clinically efficacious when readministered as an adjunct to percutaneous coronary intervention. However, concomitant heparin administration must be carefully monitored and warfarin therapy should be avoided. Vigilant surveillance for thrombocytopenia should be employed. Reduced dosing may be necessary when abciximab is readministered within days of the initial administration.

Abciximab↗
PubMed1999

Comparison of immediate and in-hospital results of conventional balloon and perfusion balloon angioplasty using intracoronary ultrasound.

Angiographic studies have demonstrated that perfusion balloon percutaneous transluminal coronary angioplasty (PTCA) may result in modestly improved luminal gains and fewer major dissections than conventional balloon PTCA. However, intracoronary ultrasound (ICUS), which is more sensitive than angiography in evaluating the incidence, extent, and severity of dissection, was not used. We randomized 48 patients with 54 coronary stenoses to conventional or perfusion balloon PTCA. Four 2-minute inflations were permitted with conventional balloon PTCA. Two 10-minute inflations were allowed with perfusion balloon PTCA. Quantitative coronary angiography and ICUS were performed before and after treatment. In-hospital clinical events were recorded. Conventional and perfusion balloon PTCA achieved similar improvements in lumen diameter (1.25+/-0.51 vs 1.28+/-0.51 mm) and reductions in percent stenosis (-45+/-21% vs -44+/-15%) by quantitative coronary angiography. Comparable gains in lumen diameter (0.62+/-0.39 vs 0.50+/-0.38 mm) and lumen area (2.70+/-1.96 vs 2.05+/-1.52 mm2) were observed on ICUS. Angiography demonstrated similar rates of any dissection (36% vs 21%) and major dissection (12% vs 7%). ICUS identified a similar incidence of any dissection (60% vs 76%) and type II dissection (52% vs 62%). The relative dissection area was also similar (9.2+/-5.6% vs 7.8+/-5.8%). One conventional balloon patient experienced postprocedural chest pain. No patient in either group died, or had myocardial infarction, abrupt closure, or urgent revascularization.

Angioplasty, Balloon, Coronary↗
PubMed1998

Quantitative coronary angiographic and intravascular ultrasound assessment of a new nonarticulated stent: report from the Advanced Cardiovascular Systems MultiLink stent pilot study.

OBJECTIVES: The purpose of this study was to evaluate the safety, feasibility, optimal deployment technique and 1-year clinical outcome for the Advanced Cardiovascular Systems (ACS) MultiLink stent. BACKGROUND: Optimal stent deployment assessed by quantitative coronary angiography and intravascular ultrasound (IVUS) is associated with improved clinical outcome. METHODS: Forty-nine consecutive patients with a discrete stenosis in a native coronary artery 3 to 4 mm in diameter were treated with the new, balloon-expandable ACS MultiLink stent. Stent expansion was assessed in all patients using quantitative coronary angiography and serial IVUS imaging after 8-, 12- and 16-atm inflations. Clinical follow-up was obtained at 30 days and 1 year. RESULTS: All 49 patients had successful placement of a MultiLink stent without death, emergency coronary artery bypass graft surgery or Q wave myocardial infarction. After placement of the MultiLink stent, the minimal lumen diameter increased from 1.24 to 2.98 mm (p < 0.001), and diameter stenosis decreased from 61% to 7% (p = 0.001). Minimal lumen cross-sectional area by IVUS increased progressively after 8, 12 and 16 atm (5.6 to 6.8 to 7.4 mm2, respectively, p < 0.001). However, only 64% of stents achieved a lumen/reference area ratio > or = 70%. No adverse clinical events occurred by 30 days, and by 1 year only one patient (2.0%) required revascularization of the stented artery. CONCLUSIONS: Treatment of stenoses in native coronary arteries with the MultiLink stent is associated with a high success rate and a low incidence of adverse events by 1 year, despite the fact that the majority of stents did not meet IVUS-defined criteria for "optimal stenting" derived from first-generation devices.

Aged↗
PubMed1998

New intracoronary stent designs: form follows function versus function follows form.

Intracoronary stenting improves the acute and long-term safety and efficacy of percutaneous coronary interventions by minimizing the risks of abrupt closure and late restenosis. Enhanced designs of new coronary stents will continue to expand the spectrum of coronary anatomy and clinical settings amenable to nonsurgical revascularization. Improvements in deliverability, application to complex lesions, and durability of results are direct effects of improved design characteristics. Future design features may also include incorporating adjunctive therapies such as antithrombotic or antiproliferative agents with stent-based delivery systems. Results of new stent registries and randomized clinical trials are reviewed.

Biocompatible Materials↗
PubMed1997

Comparison of six-month outcome of coronary artery stenting in patients <65, 65-75, and >75 years of age.

We studied 1,238 patients receiving 1,880 coronary stents. In-hospital outcomes were divided by age into <65 years (n = 747, group 1), 65 to 75 years (n = 326, group 2), and >75 years (n = 165, group 3). Procedural success was 97.2%, 95.1%, and 98.8% in groups 1, 2, and 3, respectively (p = NS). There was 1 death (group 1). Myocardial infarction occurred in 1.2%, 2.8%, and 1.8%, bypass surgery occurred in 0.9%, 1.8%, and 1.2%, and repeat balloon angioplasty in 0.3%, 0.6%, and 0% of patients in groups 1, 2, and 3, respectively (p = NS for all comparisons). Vascular complications occurred in 2.8%, 4.9%, and 6.1% in groups 1, 2, and 3, respectively (p <0.05). Six-month follow-up of patients was divided by age: <65 years (n = 564, group 1); 65 to 75 years (n = 221, group 2); and >75 years (n = 122, group 3). Event-free survival was 94.5%, 90.5%, and 89.3% for groups 1, 2, and 3, respectively (p = NS). Death occurred in 0.4%, 0.5%, and 1.6%; myocardial infarction occurred in 1.2%, 2.3%, and 1.6%, and target vessel revascularization in 4.3%, 8.6%, and 7.4% for groups 1, 2, and 3, respectively (p = NS for all comparisons). Thus, coronary stenting produced favorable in-hospital and 6-month outcomes in all 3 age groups. Age itself should not preclude patients from undergoing coronary stenting.

Age Factors↗
PubMed1997

Influence of coronary atherosclerotic remodeling on the mechanism of balloon angioplasty.

OBJECTIVES: Intracoronary ultrasonography was used to assess coronary arteries before and after balloon percutaneous transluminal coronary angioplasty (PTCA) to determine whether the mode of coronary atherosclerotic remodeling affects the mechanism of balloon dilation. BACKGROUND: Coronary arteries may enlarge or shrink in response to atherosclerotic plaque development. The effect of coronary remodeling on the mechanism of balloon PTCA has not yet been studied. METHODS: Forty-one patients with 47 native de novo coronary artery lesions were studied with a 30 MHz intracoronary ultrasound catheter before and after balloon PTCA. Images were analyzed at the lesion site and the adjacent reference segments. At each site the lumen, vessel, and plaque area and the percent area stenosis were measured. Lesions were separated into two groups based on relative vessel area (lesion vessel area/reference vessel area). A relative vessel area >1.0 defines adaptive enlargement (group 1, n = 25), whereas a relative vessel area < or =1.0 reflects coronary shrinkage (group 2, n = 22). Regression analysis examined whether elastic recoil and the PTCA balloon/vessel area ratio correlated. RESULTS: After balloon PTCA was performed, both the enlargement and shrinkage groups had similar gains in luminal area (2.3 +/- 1.8 mm2 [mean +/- SD] vs 2.8 +/- 1.7 mm2, p = 0.32), reduction in percent stenosis (-19.2% +/- 11.5% vs -14.4 +/- 12.7, p = 0.18), and final lumen area (4.9 +/- 1.7 mm2 vs 4.7 +/- 1.9 mm2, p = 0.73). However, the mechanism of luminal enlargement was different in each group. Reduction in plaque area was significantly greater in the enlargement group (group 1, -2.0 +/- 1.7 mm2 vs group 2, 0.04 +/- 2.2 mm2; p = 0.001), whereas increased vessel area was more important in the shrinkage group (group 1, 0.8 +/- 1.5 mm2 vs group 2, 2.4 +/- 2.3 mm2; p = 0.009). Positive correlation was seen between elastic recoil and the balloon/vessel area ratio in lesions with vessel enlargement (r = 0.80, p < 0.0001). No such correlation was observed in shrinkage vessels (r = 0.28, p = 0.21 ). CONCLUSIONS: The acute luminal gain after balloon PTCA is similar regardless of the type of coronary remodeling. However, the mode of remodeling affects the mechanism of balloon dilation such that enlargement vessels exhibit plaque compression, whereas shrinkage arteries demonstrate vessel stretch. The post-PTCA elastic recoil correlates linearly to the balloon/vessel area ratio in arteries that have undergone adaptive enlargement.

Angioplasty, Balloon, Coronary↗
PubMed1997

QRS changes during percutaneous transluminal coronary angioplasty and their possible mechanisms.

OBJECTIVES: The purpose of the study was to describe the configuration, and investigate the mechanisms, of QRS changes occurring during percutaneous transluminal coronary angioplasty (PTCA). BACKGROUND: QRS changes during PTCA have been attributed to both a passive ST segment shift and conduction disturbances (peri-ischemic block). The direct relation between ST segment shift and QRS changes, however, has not been established, and the definition of conduction disturbances remains to be clarified. METHODS: Twelve-lead electrocardiograms (ECGs) were recorded before PTCA, at the end of 2 min of PTCA and after return to baseline values in 29 patients (left anterior descending coronary artery [LAD] in 13 patients, right coronary artery [RCA] in 14 and left circumflex coronary artery in 2). Electrocardiographic complexes before and during PTCA were superimposed to determine the amplitudes of initial, terminal and total QRS deflection; the relations of QRS changes to baseline (TP segment) and ST segment shift; and the duration of QRS and corrected QT intervals. RESULTS. 1) The direction of the initial QRS deflection was unchanged, but changes of its amplitude occurred. 2) Terminal QRS deflection changed in all patients with a ST segment shift > 17% of the R amplitude, and the correlation between the decrease in the S amplitude and ST segment shift was significant (r = 0.9, p < 0.01) in patients with LAD PTCA. Correlation between changes in total QRS amplitude and ST segment shift in patients with RCA PTCA was weaker (r = 0.54, p = 0.056). 3) Transient conduction disturbance manifested by QRS widening in selected leads occurred in 2 of 29 patients. CONCLUSIONS. 1) Changes in terminal QRS deflection during PTCA are proportional to the magnitude of the ST segment shift. 2) Conduction disturbances manifested by increased QRS duration occurred infrequently. We suggest that the term peri-ischemic block be applied only to changes in QRS configuration associated with QRS widening.

Aged↗
PubMed1996

Late coronary artery stenosis regression within the Gianturco-Roubin intracoronary stent.

The late angiographic outcome of the Gianturco-Roubin intracoronary stent has not been well defined. To investigate serial changes within the stent, we studied 23 patients (15 men and 8 women, median age 63) who had late angiographic follow-up ( > 1 year) after undergoing Gianturco-Roubin stenting for angioplasty-associated acute or threatened native coronary artery closure. Coronary angiography before and after stenting, at 6-month follow-up, and at late return was analyzed with quantitative coronary angiography. The median time from stent deployment to late angiographic follow-up was 27 months. As expected, stenting significantly increased the median minimal lumen diameter (MLD) acutely from 1.0 to 2.46 mm. Median percent diameter stenosis decreased from 66% to 18%. Although at 6 months there was a significant loss of the acute gain (median MLD decreased from 2.46 to 1.9 mm), with a corresponding increase in percent stenosis from 18% to 31%, late angiography demonstrated lesion regression, median MLD increasing from 1.9 to 2.15 mm (p = 0.004), and percent stenosis decreasing from 31% to 21% (p = 0.0026). No patient had a significant decline in minimal lesion diameter, and 5 patients had a > 50% increase in MLD at late follow-up. Linear regression analysis of 6-month MLD and late lumen gain suggested that lesions with the greatest regression were those with the lowest lumen diameters at 6-month angiography. Late angiographic analysis demonstrated significant lesion regression within the Gianturco-Roubin stent, which was sometimes dramatic. In suggesting that coronary arteriography at 6 months may underestimate the late angiographic benefit of intracoronary stenting, these data have important clinical implications, and imply that patients with a stable clinical course and angiographic stent restenosis may often be followed rather than routinely redilated.

Angioplasty, Balloon, Coronary↗
PubMed1996

Lesion-directed administration of alteplase with intracoronary heparin in patients with unstable angina and coronary thrombus undergoing angioplasty.

Percutaneous coronary revascularization in patients with unstable angina and coronary thrombus carries a high complication rate. A new strategy to reduce thrombus burden before revascularization was tested in a multicenter prospective trial. Patients with unstable angina and coronary thrombus (n = 45) received alteplase through an infusion catheter at the proximal aspect of the target lesion and concomitant intracoronary heparin via a standard guiding catheter. Angiography was performed before and alter lesion-directed therapy and post-intervention. Systemic fibrinogen depletion and thrombin activation were not observed, while fibrinolysis was evident for > or = 4 hr after treatment. Target lesion stenosis did not change significantly after lesion-directed therapy, but thrombus score was reduced, particularly among patients who had large thrombi (mean 2.2 vs. 1.6, P = 0.02). Revascularization was successful in 89% of patients. Median final stenosis was 30% and mean final thrombus score was 0.4. Complications included recurrent ischemia (11%), MI (7%), abrupt closure (7%), severe bleeding (4%), and repeat emergency angioplasty (2%). Patients with overt thrombus appeared to derive the most angiographic benefit from lesion-directed alteplase plus intracoronary heparin. Later revascularization was highly successful. This strategy may be a useful adjunct to percutaneous revascularization for patients with unstable angina and frank intracoronary thrombus.

Adult↗
PubMed1996

Nonatherosclerotic causes of coronary artery narrowing--Part I.

Approximately 5% of patients with acute myocardial infarction do not have atherosclerotic coronary artery disease but have other causes for their luminal narrowing. The first part of this three-part review of nonatherosclerotic causes of coronary narrowing focuses on congenital coronary artery anomalies, coronary fistula, and high take-off position of coronary ostia.

Arterio-Arterial Fistula↗
PubMed1996

Nonatherosclerotic causes of coronary artery narrowing--Part III.

Approximately 5% of patients with acute myocardial infarction do not have atherosclerotic coronary artery disease but have other causes for their luminal narrowing. The third part of this three-part review of nonatherosclerotic causes of coronary narrowing focuses on coronary vasculitis, infectious diseases, Kawasaki's disease, metabolic disorders, metastatic disease, and substance abuse (cocaine).

Coronary Disease↗
PubMed1996

Abrupt (< 1 day), acute (< 1 week), and early (< 1 month) vessel closure at the angioplasty site. Morphologic observations and causes of closure in 130 necropsy patients undergoing coronary angioplasty.

While abundant clinical and angiographic data are available regarding features of acute or abrupt closure at the site of balloon angioplasty, little morphologic information is available. This study discusses morphologic-histologic causes for acute closure after angioplasty in 130 necropsy patients. Intimal-medial flaps, elastic recoil, and primary thrombosis were the three leading morphologic causes for closure. Data were subdivided into time categories: abrupt (< 1 day), acute (< 1 week), and early (< 1 month). Intimal-medial flaps remained the most common cause for angioplasty closure despite time from angioplasty to documented occlusion. Morphologic recognition of types and frequencies of angioplasty closure are discussed, and specific mechanical, pharmacologic, or combined treatments are reviewed.

Adult↗